The present invention generally relates to the electrokinetic delivery of a substance (for example, a medicament) into a treatment site, e.g., tissue and, more particularly, to systems and methods for such delivery that satisfy certain risk criteria for current leakage of medical equipment that maintains direct electrical contact with human skin, that are adaptable for large treatment areas and/or that use a convenient and low-cost arrangement of electronics. The majority of applications using the present invention are for applying medicaments to treatment sites and therefore the term medicament is sometimes used in lieu of the term substance in this description. However, the use of the term “medicament” in a particular instance is not intended to exclude the possibility of using other, non-medicament substances.
One type of electrokinetic delivery mechanism is iontophoresis. Iontophoresis is the transfer of ionic agents into tissue by means of electricity. The active component of the medicament, either directly ionizable or attached to a carrier ion and either positively or negatively charged, is driven into the tissue by a properly biased electrode through barriers to treatment sites such as animal (including human) skin, cell and mucosal membranes and other barrier surfaces. Iontophoresis has been used to deliver, among other things, morphine HCL for postoperative pain relief, topical anesthetics (such as lidocaine) for transdermal anesthetization, anti-viral agents for herpes infection, and anti-fungal medicines for onychomycosis, for example, nail bed (finger and toe) fungal infections or athlete's foot. The use of iontophoretic transdermal or transmucocutaneous delivery techniques obviates the need for hypodermic injection for many medicaments, thereby eliminating the concomitant problems of trauma, pain and risk of infection to the patient. Such delivery techniques may also be utilized for controlled or localized treatment especially when a substantial systemic involvement of the medicament is unwanted or harmful.
Regardless of the charge of the medicament to be administered, conventional iontophoretic delivery devices typically employ two electrodes (an anode and a cathode). In conjunction with the patient's skin or mucosa, the first (applicator or treatment) electrode is positioned at a treatment site on the skin or mucosa, and the second (counter) electrode is affixed to a second site on the skin or mucosa. These electrodes form a current path that enhances the rate of penetration of the medicament into the treatment site adjacent to the applicator electrode. A conventional iontophoretic delivery system 100 is shown in FIG. 1. System 100 includes a treatment electrode (anode) 102 and a counter electrode (cathode) 104 connected to a DC power supply 106. Electrodes 102 and 104 are in electrical contact with the skin or mucosa via conductive layers 110 and 112, respectively. Such layers may be part of a single medicament-carrying substrate. The medicament-carrying substrate is generally disposable and non-reusable and may be releasably adherable to the patient's treatment site and/or to electrodes 102 and 104 or merely interposed in between treatment site and electrodes. Conductive layers 110 and 112 are shown in FIG. 1 as comprising a medicine-soaked sponge (e.g., a morphine HCL-soaked sponge) and a saline-soaked sponge, respectively. In use, iontophoretic device 100 is turned on (e.g., by a switch, not shown) and a current flows from treatment electrode 102, through conductive layer 110 and skin plus underlying tissue 108, to counter electrode 104, thereby driving medicament through the treatment site into the skin and underlying tissue.
Although use of alternating current has been reported (see, e.g., U.S. Pat. No. 5,224,927 to Tapper, Jul. 6, 1993), direct current is generally preferred in iontophoresis. As set forth in the '927 patent, at AC frequencies higher than approximately 10 Hz, no substantial effective drug delivery takes place. Medicament and other ions merely move to and fro, lacking any net unidirectional movement. For DC iontophoresis, the amount of current used varies from 0.2 to 1 milliampere, which exceeds the risk-current limit of 10 microamperes established for current leakage of medical equipment that maintains direct electrical contact with the patient. There exists, therefore, a potential hazard associated with ventricular fibrillation and cardiac arrest if the current generated during iontophoresis accidentally passes through the patient's heart. In iontophoresis, the rate of drug delivery increases with current. For this reason, higher current is, in principle, always favored because treatment time is proportionally reduced. However, for current exceeding 0.5 to 1 milliampere, the patient may feel an uncomfortable burning sensation. Even at the 0.5 to 1 milliampere range, when the treatment area is relatively small, the resulting high current density can possibly cause pain and burning and destruction of the skin tissue.
In any case, to remain effective, existing iontophoresis devices may use treatment currents exceeding the established risk-current limit for equipment leakage. In order to reduce the ventricular fibrillation risk, some devices limit the separation distance between the treatment and the counter electrode so that the heart is not directly in the current path and is therefore less likely to be included within the fringe electric fields created by the electrodes. However, because electric current always flows through a path of least resistance, i.e., a path of shorter distance along the skin, the electrode separation distance needs to be large enough so that current is not short-circuited or concentrated between proximal edges of the electrodes (i.e., between edges 120 and 130 in FIG. 1), so that the current distribution under the treatment electrode is relatively uniform for effective drug delivery, and so that there are no hot-spots or areas of high current density to cause discomfort and pain. Some iontophoretic devices use a large separation distance to obtain a more uniform current distribution by placing the counter electrode in a less accessible and awkward location such as the back or the rear shoulder of the patient.
An effective method for self-administration of a medicament into an individual's skin is disclosed in U.S. Pat. No. 5,676,648 and uses a small cylindrical probe in which the treatment applicator electrode is located at the distal end of a counter electrode consisting of a circumferential tactile metal band which provides electrical connection to the individual's finger and hand. The individual's body completes a long electrical circuit path (through the arm and torso), and thus a uniform current distribution and effective medicament delivery is assured.